The objectives of this proposal are to study the role of endothelium (EC) in the pathophysiologic sequence of acute respiratory failure (ARF) and secondly to examine the relationship of pulmonary failure and cardiac function. We will examine the functional characteristics of EC both as a semipermeable membrane as well as a metabolic regulator before, during and after ARF. The metabolic activity of EC will be assayed primarily by measuring serotonin (5-HT) transport. Several in-vitro EC systems will be used to characterize the biochemistry of 5-HT transport and the mechanisms of reduced or blocked transport in pathologic states. The sequelae of EC damage and the loss of metabolic regulating activity may be increased levels of circulating vaso and broncho active materials. These materials will be measured by bioassay and their interaction with EC investigated. The systemic consequences of the failure of pulmonary metabolic regulatory activities will be studied by relating the measured levels of circulating vasoactive materials to alterations in myocardial performance. Two other areas of cardio-pulmonary interrelationships will be explored. Positive end-expiratory pressure and a varient of this breathing pattern will be analyzed regarding advantages to the heart and lungs. Fluid therapy will be similarly analyzed.